Decorin activates the epidermal growth factor receptor and elevates cytosolic Ca2+ in A431 carcinoma cells.
Several independent lines of evidence have implicated decorin, a small leucine-rich proteoglycan, in the inhibition of cell proliferation. However, the mechanism by which decorin mediates its effect on cell proliferation is unclear. Here we report, for the first time, decorin-mediated increases in intracellular Ca2+ levels of single A431 cells. The effects of decorin persisted in the absence of extracellular Ca2+ but were blocked by AG1478, an epidermal growth factor (EGF)-specific tyrosine kinase inhibitor, and by down-regulation of the EGF receptor. The effects of decorin were not mimicked by the structurally homologous protein, biglycan. Our results indicate a novel action of decorin on the EGF receptor, which results in mobilization of intracellular Ca2+ providing a possible mechanism by which decorin causes growth suppression.
Patel
S
S
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Santra
M
M
McQuillan
D J
DJ
Iozzo
R V
RV
Thomas
A P
AP
D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D003600:Cytosol / Q000378:metabolism*; D058575:Decorin; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D011509:Proteoglycans / Q000502:physiology*; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D020032:Tyrphostins
C546878:DCN protein, human; D058575:Decorin; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D009570:Nitriles; D011509:Proteoglycans; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D066246:ErbB Receptors; D002118:Calcium